Matching Items (7)
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- All Subjects: Alzheimer's Disease
- Creators: Mastroeni, Diego
Does assisted cycle therapy influence activities of daily living in older adults with Down syndrome?
Description
The aim of this study is to examine the relationship between Assisted Cycle Therapy, leisure time activity levels, fine motor control, and grip force in older adults with Down syndrome (DS), all of which affect activities of daily living (ADL) and therefore quality of life. This is relevant because this particular group is at risk for developing early onset Alzheimer's disease (AD), which presents itself uniquely in this population. The parent or guardian of six participants with DS completed Godin's Leisure Time Exercise Questionnaire and the participants themselves completed Purdue Pegboard and grip force assessments before and after an 8-week exercise intervention. The results were inconsistent with past research, with no change being seen in fine motor control or grip force and a decrease being seen in leisure activity. These findings are indicative of the importance of the effect of fatigue on leisure activity as well as maintaining elevated heart rate throughout exercise interventions.
ContributorsGomez, Elizabeth Danielle (Author) / Ringenbach, Shannon (Thesis director) / Coon, David (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
The nuclear pore complex is a structure that is found in the nuclear envelope. The nuclear pore complex is made of proteins known as nucleoporins, or Nups. There are many classes of Nups, one of which is Nups with phenylalanine-guanine repeats (FG-Nups). The FG-Nups help control the transport of material through the nuclear pore complex. One type of FG-Nup is NupL2. Previous mRNA data have shown that there is lower expression of NupL2 in Alzheimer's Disease brains than there is in control brains. However, these data are specific to mRNA expression, and do not necessarily extend to NupL2 protein levels. This study focuses on NupL2 levels in non-diseased samples and Alzheimer's Disease samples. Immunohistochemistry (IHC) with 3,3'-diaminobenzidine was performed on temporal neo-cortical brain tissue. Western blots were also performed to quantify the protein levels in non-diseased samples and Alzheimer's Disease samples, and were completed using middle temporal gyrus lysates. The IHC results show that there is more NupL2 protein expression in non-diseased samples than there is in Alzheimer's Disease samples. Likewise, the western blot data show higher NupL2 protein levels in non-diseased samples than in Alzheimer's Disease samples. Both the IHC data and the western blot data indicate that there are higher NupL2 expression levels in non-diseased samples than in Alzheimer's Disease samples. Decreased NupL2 expression in Alzheimer's Disease may indicate that it is not functioning properly. This could lead to the leaking of material between the nucleoplasm and the cytoplasm, which may in turn contribute to Alzheimer's Disease pathogenesis.
ContributorsKulkarni, Neha Uday (Author) / Coleman, Paul (Thesis director) / Mastroeni, Diego (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases worldwide, with no effective treatments or preventions. Evidence suggests that environmental factors, including dietary nutrients, contribute to the etiology of AD. Choline is an essential nutrient found in many common foods. Choline is produced endogenously, but not at levels sufficient for healthy metabolic function and thus requires dietary supplementation. Literature shows that ~90% of Americans do not meet the adequate intake threshold for dietary choline consumption and therefore are dietary choline-deficient. While dietary choline supplementation throughout life has been shown to have significant health benefits, such as reducing AD pathology and improving cognition in a mouse model of AD, the impacts of dietary choline deficiency are unknown. Experiments were designed to understand the effects of dietary choline deficiency in healthy, non-transgenic mice (NonTg) and in the 3xTg-AD mouse model of AD. From 3 to 12 months of age, mice received either adequate choline (ChN) in the diet or were put on a choline-deficient (Ch-) diet. A Ch- diet leads to significant weight gain throughout life in both the NonTg and 3xTg-AD mice, with AD mice showing a greater increase. Additionally, impaired glucose metabolism, which is a risk factor for AD, was induced in both NonTg Ch- and 3xTg-AD Ch- mice. Interestingly, Ch- induced cardiomegaly in 3xTg-AD mice and elevated markers of cardiac dysfunction in NonTg mice to similar levels in 3xTg-AD mice. Finally, Ch- exacerbated amyloid-β plaque pathology and tau hyperphosphorylation in the hippocampus and cortex of 3xTg-AD mice. Proteomic analyses revealed Ch- induced changes in hippocampal proteins associated with postsynaptic receptor regulation, microtubule stabilization, and neuronal development, as well as well-known AD-associated proteins (MAPT, BACE1, MECP2, CREBBP). Proteomic analyses also revealed Ch- induced changes of plasma proteins associated with secondary pathologies of AD including inflammation, immune response insulin metabolism, and mitochondrial dysfunction (SAA1, SAA2, IDE, HSPD1, VDAC-1, VDACE-2). Taken together, these data suggest that dietary choline deficiency induces system-wide cellular and molecular dysfunction associated with AD across several pathogenic axes, through proteomic changes not only in the hippocampus but also in the plasma.
ContributorsDave, Nikhil (Author) / Velazquez, Ramon (Thesis advisor) / Piras, Ignazio (Committee member) / Mastroeni, Diego (Committee member) / Arizona State University (Publisher)
Created2022
Description
Neuroinflammation contributes significantly to the pathogenesis of Alzheimer’s and Parkinson’s diseases. However, the inflammatory pathways contributing to neurodegeneration are not well understood. Moreover, there is a need to identify changes in inflammatory signaling that may occur early in disease progression to identify potential targets for therapeutic intervention. An important step towards addressing this need is understanding how the extracellular vesicles (EVs) released by microglia can be detected in the periphery. For microglia, phagocytic macrophages, and CD 14+ monocytes share many genes and membrane- bound proteins, and there is currently no method to distinguish microglia EVs from those generated by macrophages or monocytes. Therefore, this study aims to identify membrane-bound proteins unique to microglia EVs to enable their reliable isolation. Liquid-chromatography tandem mass spectrometry analysis was used to detect proteins in the EVs from both normal and disease-associated human stem-cell differentiated microglia (iMGL), and human induced pluripotent stem cell-derived CD 14+ monocytes and macrophages. We identified 23 proteins unique to the microglial EVs, eight of which localize to the membrane and may be potential targets for isolation. This investigation also used RNA sequencing to gain insight into the contents of DAM-like and control iMGL EVs and of microglia and white blood cells in Alzheimer’s disease. We propose that the contents of microglial EVs isolated from peripheral compartments will provide crucial insight for understanding the current inflammatory state of CNS microglia. This approach could provide a means to track changes in microglial activation over time, which is critical for understanding the progression of neuroinflammatory diseases like Alzheimer's and Parkinson's. Additionally, it may offer insights into potential therapeutic targets for modulating neuroinflammation.
ContributorsLopatin, Ulia (Author) / Mastroeni, Diego (Thesis director) / Velazquez, Ramon (Committee member) / Van Keuren-Jensen, Kendall (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
Dementia is a collective term used to describe symptoms of cognitive impairment in learning and memory. The most prevalent form of dementia is Alzheimer’s disease (AD). In order to understand the pathological mechanisms associated with AD, animal models have been created. These various mouse models replicate the pathology found in humans with AD. As a consequence of the fact that this disease impairs cognitive abilities in humans, testing apparatuses have been developed to measure impaired cognition in animal models. One of the most common behavioral apparatuses that has been in use for nearly 40 years is the Morris water maze (MWM). In the MWM, animals are tasked to find a hidden platform in a pool of water and thereby are subjected to stress that can unpredictably influence cognitive performance. In an attempt to circumvent such issues, the IntelliCage was designed to remove the external stress of the human experimenter and provide a social environment during task assessment which is fully automated and programable. Additionally, the motivation is water consumption, which is less stressful than escaping a pool. This study examined the difference in performance of male and female cohorts of APP/PS1 and non-transgenic (NonTg) mice in both the MWM and the IntelliCage. Initially, 12-month-old male and female APP/PS1 and NonTg mice were tested in the hippocampal-dependent MWM maze for five days. Next, animals were moved to the IntelliCage and underwent 39 days of testing to assess prefrontal cortical and hippocampal function. The results of this experiment showed significant sex differences in task performance, but inconsistency between the two testing paradigms. Notably, males performed significantly better in the MWM, which is consistent with prior research. Interestingly however, APP/PS1 females showed higher Amyloid-β plaque load and performed significantly better in the more complex tasks of the IntelliCage. This suggests that Aβ plaque load may not directly contribute to cognitive deficits, which is consistent with recent reports in humans with AD. Collectively, these results should inform scientists about the caveats of behavioral paradigms and will aid in determining translation to the human condition.
ContributorsMifflin, Marc Anthony (Author) / Velazquez, Ramon (Thesis director) / Mastroeni, Diego (Committee member) / School of Geographical Sciences and Urban Planning (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder characterized clinically by memory loss, confusion and pathologically by the presence of amyloid beta plaques and neurofibrillary tangles. Even though anti-amyloid vaccination clinical trials have removed amyloid plaques, clinical efficacy has not been achieved during the early phases of AD suggesting that other mechanism play a role in the dementia associated with AD. Mutations in nucleoporin genes have been linked to various human diseases including neurological, nephrotic, cardiac, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). A recent study found mislocalization of NUP98 and NUP62 in the cytoplasm of human hippocampal neurons in AD (Eftekharzadeh et al., 2019). These NUP’s were associated with phosphorylated-tau, suggesting the depletion of nucleoporins from the nuclear envelope potentially having a direct interaction with phospho-tau. The present study investigated the three differentially expressed NUPs (NUP-214, -93, -153) from different parts of the NPC (cytoplasmic filaments, inner ring structure, nuclear basket) using immunohistochemistry and immunoblotting procedures. This investigation represents one of the first attempts to categorize differential structural changes throughout the NPC in AD.
ContributorsGoras, Miriam (Author) / Coleman, Paul (Thesis director) / Mastroeni, Diego (Committee member) / Mufson, Elliott (Committee member) / Barrett, The Honors College (Contributor) / Microbiology (Contributor)
Created2022-05
Description
Alzheimer’s Disease (AD) is one of the most common forms of dementia and a major cause of disability and dependency in older patients worldwide.Although there has been a lot of research done in the field of gene expression and possible drivers of AD, there has not been enough investigation into transcription start site and alternative promoter usage of AD.
With relatively small genomes, species have evolved mechanisms for diversifying their transcriptome, which is the set of messenger mRNA transcripts produced in a given cell.
While the most well-known mechanism of diversification is alternative splicing, another mechanism that has been less explored is alternative promoter (AP) usage, which generates different transcripts by selecting different transcription start sites (TSSs) upstream of a gene.
More importantly, AP usage can bring about different coding sequences, which can in some cases lead to changes within the N-termini of the cognate proteins.
Alternative promoter usage has the potential to regulate processes like alternative splicing, tissue specificity, regional specificity and subcellular specificity of gene expression and gene activation during development.
In this study a customized pipeline for STRIPE-seq generated data was applied to AD and control data set and the first AD promoter atlas was generated.
This atlas was used to generate list of genes with differentially used TSRs and biological pathways they are involved in.
Finally, a consensus cluster set was created to investigate alternative promoter usage in AD patients and alternative promoter usage was shown in Alzheimer’s Disease related genes such as APOE and MAPT.
ContributorsStampar, Mojca (Author) / Lee, Heewook (Thesis advisor) / Raborn, Randolph T (Committee member) / Mastroeni, Diego (Committee member) / Arizona State University (Publisher)
Created2022